almost quantitative t-PA entrapment in liposomes can be achieved by selecting the proper milieu and inducing a strong interaction between t-PA and bilayer.

Two principle techniques exist for process safety in the chemical industry; these methods are based on the maintenance of either reaction conditions or chemical/physical stability in order to provide a safe working environment. From experience gained in the manufacture of organic peroxides, it is concluded that the latter technique (intrinsic continuous process safety), aiming at prevention, is to be preferred. Intrinsic continuous process safety is based on the stability of the reaction system and reaction conditions and minimizes the possibility of dangerous occurrences resulting from human error or equipment failure. Qualitative and quantitative hazard analysis is used to determine conditions for chemicaVphysical stability of a system. A flow calorimeter suitable for evaluation of thermochemical characteristics of the reaction system is described. Process research, process development, and safety research should cooperate closely on process safety aspects from the start of the R & D synthetic work.

Glucosamine (UDP-N-Acetyl)-2-Epimerase and N-Acetylmannosamine Kinase (GNE) is the rate-limiting enzyme in the synthesis of sialic acid. Mutations in the GNE gene are associated with adult-onset myopathy. Recently, four GNE variants were identified in patients with congenital macrothrombocytopenia. The relationship between GNE mutations and macrothrombocytopenia is incompletely understood, as most myopathy patients have normal platelet counts. Here, we investigated the molecular mechanism underlying GNE-related thrombocytopenia. We identified 2 female siblings with a severe congenital macrothrombocytopenia, a severe bleeding pattern and a homozygous p.R420Q mutation in the GNE gene. Functional characterization of the 420Q-GNE variant confirmed loss of function. Patient platelets showed hyposialylation, but plasma markers for glycosylation were normal. 111 Indium-labeled autologous platelet scanning in one patient indicated hepatic platelet sequestration and a decreased platelet half-life. Consistent with these findings, uptake of patient platelets by THP-1 macrophages and HepG2 liver cells was strongly increased. One patient was treated with romiplostim, which increased the platelet count and ameliorated the bleeding tendency. In conclusion, this study shows that the 420Q-GNE variant results in hyposialylation of glycans on platelets, which leads to rapid clearance by the liver and causes thrombocytopenia. Bleeding symptoms can be treated with romiplostim.

Use of a positively charged enhancer may improve J(ss) of anionic macromolecular penetrants during passive and iontophoretic delivery. On-line visualisation of iontophoresis across SC was possible and can provide mechanistic insight into SC transport pathways.

A multitude of samples is required to monitor and optimize the quality and reliability of quantitative measurements of (super-resolution) light microscopes. Here, we present a single sample to calibrate microscopes, align their laser beams and measure their point spread function (PSF) in 3D. The sample is composed of a refractive index matched colloidal crystal of silica beads with fluorescent and gold cores. The microscope can be calibrated in three dimensions using the periodicity of the crystal; the alignment of the laser beams can be checked using the reflection of the gold cores; and the PSF can be measured at multiple positions and depths using the fluorescent cores. It is demonstrated how this sample can be used to visualize and improve the quality of confocal and super-resolution images. The sample is adjustable to meet the requirements of different NA objectives and microscopy techniques and additionally can be used to evaluate refractive index mismatches as a function of depth quantitatively.